Application of Diagnostic Stewardship to Fungal Polymerase Chain Reaction: Low Yield of Follow-up Testing on Plasma and Bronchoalveolar Lavage After a Negative Result.

BACKGROUND: Early diagnosis of invasive fungal disease is essential for optimizing management. Although the clinical utility of fungal polymerase chain reaction (PCR) testing on plasma and bronchoalveolar lavage (BAL) has been established, the role of follow-up testing remains unclear. METHODS: This was a retrospective single-center study. The yield of follow-up PCR for Aspergillus species, Mucorales agents, Fusarium species, Scedosporium species, dimorphic fungi, Pneumocystis jirovecii, and Candida species on plasma and/or BAL was measured at intervals of 1, 2, 3, and 4 weeks following a negative result. RESULTS: A total of 1389 follow-up tests on 406 plasma specimens from 264 patients and 983 BAL specimens from 431 patients were evaluated. Overall, the positivity rate at 1, 2, 3, and 4 weeks was 2.7% (4/148), 3.3% (4/123), 5.1% (4/78), and 3.5% (2/57), respectively, on plasma, and 0% (0/333), 0.3% (1/288), 0.4% (1/228), and 0.7% (1/134), respectively, on BAL. Conversions occurred with Aspergillus species, Mucorales agents, and Fusarium species PCR on plasma and Aspergillus species and P jirovecii PCR on BAL. All patients who converted were immunocompromised. Within 1 week of a prior negative test, 2 Aspergillus and 2 Mucorales PCRs were positive on plasma, and zero tests were positive on BAL. In week 1, only 1 Aspergillus species that was positive on day 7 was classified as probable fungal disease. CONCLUSIONS: Fungal PCR follow-up testing on plasma and BAL within 4 weeks of a prior negative result was of low yield and rarely generated a positive result considered clinically significant in the first week.

Evaluating amikacin minimum inhibitory concentration in trailing growth for Mycobacterium avium complex.

BACKGROUND: Amikacin is a first-line drug that must be evaluated when performing an antimycobacterial susceptibility test (AST) for Mycobacterium avium complex (MAC). However, the presence of sporadic trailing growth in MAC makes determining the precise point for reading its minimal inhibitory concentration (MIC) challenging. METHODS: Susceptibility was re-tested for 134 MAC clinical isolates using the Sensititre SLOMYCOI panel, the rrs gene was sequenced, and amikacin exposure history was investigated. The MIC50, MIC90, and the epidemiological cut-off value (ECOFF) were calculated using the EUCAST method. RESULTS: After re-testing and ignoring trailing growth, of the 22 M. intracellulare isolates originally classified as resistant to amikacin according to the CLSI guideline, 10 strains were reclassified as intermediate and four as susceptible. Similarly, from the seven resistant M. avium strains, one was reclassified as intermediate and four as susceptible. No rrs gene mutations were detected in any isolates, including resistant strains. When ignoring trailing growth, the calculated MIC50, MIC90, and ECOFF values closely aligned with the EUCAST MIC distribution. CONCLUSION: To maintain the current CLSI breakpoint, trailing growth should be ignored when reading the amikacin MIC of MAC. To read the MIC at complete bacterial inhibition, the CLSI breakpoint needs to be raised.

Rare Case of Accelerated-Phase Chronic Myeloid Leukemia Diagnosed During Treatment for JAK2 V617F-Positive Primary Myelofibrosis.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the expansion of myeloid lineage cells. Chronic myeloid leukemia (CML) is characterized by a BCR-ABL1 fusion gene that causes constitutive tyrosine kinase activity. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis (PMF) are frequently associated with driver mutations in genes such as JAK2, CALR, and MPL and are mutually exclusive of BCR-ABL1. Herein, we report the first case study of a patient diagnosed with accelerated-phase CML while undergoing treatment for initial JAK2 V617F-positive, BCR-ABL1-negative PMF. This finding emphasizes the importance of BCR-ABL1 testing in patients with an atypical BCR-ABL1-negative MPN disease course.